Atazanavir and drug-drug interactions
Posted: Jul 15, 2003
QUESTION:
I have a patient who started Atazanavir,300mgqd/Ritonavir,100mg-qd/Efavirenz,600mg-qd/Tenofovir,300mg-qd/Didanosine,250mg-qd.
(N.B.Ritonavir was added to compensate for ATZ-EFV interaction, and ddI dose was decreased by 1/2 and is taken 12 hours apart from TNF to compensate for ddI-TNF interaction.) Patient began regimen 12/10/02 on ATZ-expanded access program and achieved viral load <50 by 01/07/03. Patient remains undetecable and likes the regimen. Now, the company is hinting that tenofovir may affect atazanavir levels and a dose adjustment may be needed, however, they aren't permited to give advice as how this dose adjustment should be made.
1. If this were your patient, what would you do?
2. What would you do in a patient where the only drug-drug interaction is ATZ/TNF?
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RESPONSE FROM: 
From the available data, it seems that while TDF reduces drug exposure to atazanavir, the boosting of the later with ritonavir raises drug exposure to the point where the drug-drug interaction effect is minimal-- that is to say that drug trough levels still exceed the inhibitory concentration of HIV. How this particular two drug interaction relates to the interaction with efavirenz is not studied, though clearly relevant. Personally, I tend to avoid such uncharted pharmacodynamic waters until there is substantial efficacy data, or use them only in patients where other more studied options are not feasible. So, while long-term efficacy data are yet lacking on the boosted atazanavir or TDF-atazanavir interaction, on first premise this seems ok.
For your specific question, for the ATV/TDF interaction- I would only use this combination in a boosted fashion (ATV-300 mg/ ritonavir 100 mg ) if I was forced to use it. Bear in mind that there is the possibility that the boosting of ATV could result in increased bilirubin and/or lipids-- making the regimen either less attractive or potentially more toxic-- again, data is lacking, but should be forthcoming.
As for the ddI-TDF interaction, recent evaluations continue to be supportive, though again, there are litte long-term efficacy or safety data on the combination. Presented data also show that there is little additional benefit in separating the two doses in time (with or without regard to meals), allowing a much more simplified dosing regimen.
Overall, it would seem to me that you might very well be able to dose all of these medications together as a potent, once-daily, three-class regimen. BY
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